title: The hutterite variant of Treacher Collins syndrome: a 28-year-old story solved.
abstract: Treacher Collins syndrome (TCS), the best known form of mandibulofacial dysostosis (MFD) comprises a recognizable pattern of anomalies. In 1985, Lowry et al. reported on two Hutterite sisters born to apparently unaffected parents with TCS, raising the possibility of an autosomal recessive (AR) variant of TCS, subsequently given a unique Mendelian Inheritance of Man (MIM) number (248390). Recently, biallelic mutations in POLR1C were found in TCS patients, confirming AR TCS as a distinct entity. The Hutterites, an endogamous Anabaptist group, like other genetically isolated populations, provide a powerful resource for mapping AR disorders. We elected to study the molecular basis of TCS in the Hutterite population including the original kindred described in 1985, and another unrelated Hutterite patient. Prior to starting this study, a TCOF1 mutation had apparently been excluded in the original family at two outside institutions. We hypothesized that an AR variant of TCS was present in the three Hutterite patients, but homozygosity mapping did not show convincing evidence of shared regions between the affected individuals. TCOF1 analysis was undertaken and mutations were found in the three affected patients and an unaffected parent. These data show that the initial Hutterite family reported with AR TCS in fact has classic TCS due to a TCOF1 mutation, despite recent data confirming the existence of AR TCS in other populations. These results have significant counseling implications for the affected families in the Hutterite population and in the population at large. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, AB, Canada; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
authors.forename: Oana
authors.initials: O
authors.lastname: Caluseriu
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lowry
authors.forename: Ross
authors.initials: R
authors.lastname: McLeod
authors.forename: Ryan
authors.initials: R
authors.lastname: Lamont
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.forename: Francois P
authors.initials: FP
authors.lastname: Bernier
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019066:Facies; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human
keywords: Treacher Collins syndrome; mandibulofacial dysostosis